Abstract：
:A series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the MIC80, the concentration which inhibits 80% or 12 of the serotypes tested, was determined. Homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity with increased chain length. Introduction of hydrophilic groups in this position rendered the compounds inactive. Increasing the length of the side chain attached to the isoxazole ring resulted in an increase in activity. Replacement of the methyl with alkoxyalkyl substituents retained activity; however, introduction of a hydroxyl group on to the side chain reduced activity. Compound 8a, where both the isoxazole and oxadiazole rings were substituted with methyl groups, was one of the most active compounds in the series. A comparison was made between 8a and the two isomeric oxadiazoles 41 and 46, and an attempt was made to explain the difference in activity by examining electrostatic potential maps and by an energy profiling study. No conclusive results were obtained from these studies.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Diana GD,Volkots DL,Nitz TJ,Bailey TR,Long MA,Vescio N,Aldous S,Pevear DC,Dutko FJdoi
10.1021/jm00041a022subject
Has Abstractpub_date
1994-07-22 00:00:00pages
2421-36issue
15eissn
0022-2623issn
1520-4804journal_volume
37pub_type
杂志文章abstract：:Human African trypanosomiasis is causing thousands of deaths every year in the rural areas of Africa. In this manuscript we describe the optimization of a family of phtalazinone derivatives. Phosphodiesterases have emerged as attractive molecular targets for a novel treatment for a variety of neglected parasitic disea...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00985
更新日期：2020-04-09 00:00:00
abstract：:The 6-aminoglucosamine ring of the aminoglycoside antibiotic neomycin B (ring II) was conjugated to a 16-mer peptide nucleic acid (PNA) targeting HIV-1 TAR RNA. For this purpose, we prepared the aminoglucosamine monomer 15 and attached it to the protected PNA prior to its cleavage from the solid support. We found that...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300253q
更新日期：2012-07-12 00:00:00
abstract：:Procedures were developed for the synthesis of exo-(2'-chloro-5-pyridinyl)-7-(endo and exo)-amino[2.2.1]heptanes (3a and 3b). The compounds were evaluated for binding to the alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs), for pharmacological activity in the mouse tail-flick and hot-plate assays, and...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm058243v
更新日期：2005-11-17 00:00:00
abstract：:Building on the previously and successfully applied hypothesis that stereochemical complication in the proximity of the critical cationic head of a cholinergic agonist would result in subtype selective compounds, we synthesized a series of chiral derivatives of furmethide and 5-methylfurmethide, with the aim of obtain...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800145d
更新日期：2008-07-10 00:00:00
abstract：:Guanidinothiazolecarboxamides (GTCs) are a novel class of antitumor agents found to be systemically active against experimental pulmonary metastases of 3LL Lewis lung carcinoma. A series of substituted benzothiazole GTCs were found to produce enhancement of survival in this model by using 8 days of intraperitoneal dos...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00111a009
更新日期：1991-07-01 00:00:00
abstract：:A novel method, total pharmacophore diversity (ToPD), based on known pharmacophore features for numerically defining molecular similarity or diversity is described. The method captures the 3D shape and functionality of molecules by the analysis of relevant intramolecular distances to generate a short and descriptive p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010036h
更新日期：2001-10-25 00:00:00
abstract：:A six-stage stereoselective synthesis of indanyl-7-(3'-pyridyl)-(3R,6R,7R)-2,5-diketopiperazines oxytocin antagonists from indene is described. SAR studies involving mono- and disubstitution in the 3'-pyridyl ring and variation of the 3-isobutyl group gave potent compounds (pK(i) > 9.0) with good aqueous solubility. E...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201287w
更新日期：2012-01-26 00:00:00
abstract：:In an effort to determine the stereochemical requirements for pharmacological activity among the series of nonclassical cannabinoids synthesized at Pfizer, we have studied the conformational properties of the parent bicyclic analog CP-47,497. For this study, we have used a combination of solution NMR and theoretical c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00036a006
更新日期：1994-05-13 00:00:00
abstract：:1-(Benzoyloxy), 1-(4-nitrobenzoyloxy), and 1-(3,5-dinitrobenzoyloxy) derivatives of 3-fluoro-, 3-chloro-, and 3-bromopropan-2-one were prepared by oxidation of the 1-benzoyloxy-3-halopropan-2-ols in turn prepared from the appropriate benzoyl chloride and 3-halo-1,2-propanediols, 1-Benzoyloxy-3-fluoropropan-2-one was a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00215a005
更新日期：1977-05-01 00:00:00
abstract：:The synthesis and biological activity of a novel cyclic beta-sheet-type antimicrobial dehydropeptide based on gramicidin S (GS) is described. The GS analogue, containing two (Z)-(beta-3-pyridyl)-alpha,beta-dehydroalanine (DeltaZ3Pal) residues at the 4 and 4' positions (2), was synthesized by solution-phase methodologi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061051v
更新日期：2006-12-28 00:00:00
abstract：:A series of N-aryl-N'-(2-chloroethyl)ureas (CEUs) and derivatives were synthesized and evaluated for antiproliferative activity against a wide panel of tumor cell lines. Systematic structure--activity relationship (SAR) studies indicated that: (i) a branched alkyl chain or a halogen at the 4-position of the phenyl rin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0010264
更新日期：2001-03-01 00:00:00
abstract：:Forty-eight cationically substituted pentamidine congeners possessing benzofuran rings were synthesized by a copper mediated heteroannulation of substituted o-iodophenols with phenyl acetylenes. Activities of compounds 1-48 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cyto...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9006406
更新日期：2009-09-24 00:00:00
abstract：:As a continuation of our efforts to develop innovative ligands for D(3), 5-HT(1A), and 5-HT(2A) receptors with low propensity to block hERG channels, we propose a series bishetero(homo)arylpiperazines 5a-m as novel and potent multifunctional ligands characterized by low occupancy at D(2) and 5-HT(2C) receptors. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100294b
更新日期：2010-06-24 00:00:00
abstract：:A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-positi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0611509
更新日期：2007-03-08 00:00:00
abstract：:Here, we show that four chemically divergent approved drugs reported to inhibit Ebolavirus infection, benztropine, bepridil, paroxetine and sertraline, directly interact with the Ebolavirus glycoprotein. Binding of these drugs destabilizes the protein, suggesting that this may be the mechanism of inhibition, as report...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01249
更新日期：2018-02-08 00:00:00
abstract：:The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted) have been prepared, purified, and spectroscopically characterized. The water so...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00085a008
更新日期：1992-04-03 00:00:00
abstract：:N-Aminated nucleoside complexes of cis-dichloroplatinum(II) were synthesized, and their antitumor activities against L1210 cells in mice and in vitro were studied. While the native nucleosides failed to show any antitumor activity, the complexes exhibited high antitumor activity and had no nephrotoxicity in mice. Stud...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00370a006
更新日期：1984-04-01 00:00:00
abstract：:A series of analogues of buspirone was synthesized in which modifications were made in the aryl moiety, alkylene chain length, and cyclic imide portion of the molecule. These compounds were tested in vitro for their binding affinities to rat brain membrane sites labeled by either the dopamine antagonist [3H]spiperone ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00356a014
更新日期：1983-02-01 00:00:00
abstract：:4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00173a017
更新日期：1990-11-01 00:00:00
abstract：:The tetrapeptide sequence His-Phe-Arg-Trp, derived from melanocyte-stimulating hormone (alphaMSH) and its analogs, causes a decrease in food intake and elevates energy utilization upon binding to the melanocortin-4 receptor (MC4R). To utilize this sequence as an effective agent for treating obesity, we improved its me...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701093y
更新日期：2008-02-28 00:00:00
abstract：:The in vivo antitumor activity and in vitro metabolic dealkylation have been measured for an homologous series of 3-alkyl-1-(4-carbamoylphenyl)-3-methyltriazenes and have been compared with their partition coefficients. This investigation has shown that the extent of oxidative metabolism in vitro and the antitumor act...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00373a011
更新日期：1984-07-01 00:00:00
abstract：:A series of N alpha-(arylsulfonyl)-L-arginine amide derivatives with substituted or unsubstituted naphthalene and heterocyclic compounds as the N alpha-substituent was prepared and tested as inhibitors of the clotting activity of thrombin. N-n-Butyl and N-n-butyl-N-methyl derivatives of N alpha-dansyl-L-arginine amide...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00182a004
更新日期：1980-08-01 00:00:00
abstract：:A novel series of 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues has been prepared to probe the steric and electronic properties of the binding pocket of the MT(2) receptor accommodating the "out-of-plane" substituent of MT(2)-selective antagonists. The acetamide (6b) bearing an usubstituted indoline moiety ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800974d
更新日期：2009-02-12 00:00:00
abstract：:A recently discovered and structurally distinct class of antiepileptic drugs is the (arylalkyl)imidazoles. Two independently discovered representatives of this class, denzimol (alpha-[4-(2-phenylethyl)phenyl]-1H-imidazole-1-ethanol) and nafimidone (2-(1H-imidazol-1-yl)-1-(2-naphthalenyl)ethanone), are undergoing clini...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00159a004
更新日期：1986-09-01 00:00:00
abstract：:A series of water-soluble fullerene C(60) derivatives has been investigated for their cytotoxic and hemolytic properties, with the aim to correlate structure with toxicity. We observed that cationic chains induce significant toxicity while the presence of neutral or anionic moieties did not produce any response in our...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0497489
更新日期：2004-12-30 00:00:00
abstract：:Gossypol and 17 derivatives were tested as inhibitors of aldose reductase from human placenta. Gossypol and a number of the derivatives were potent inhibitors. The order of inhibitory activity was interpreted in relation to the Kador-Sharpless pharmacophor model for the aldose reductase inhibitor site. The structural ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00115a021
更新日期：1991-11-01 00:00:00
abstract：:Matrix metalloprotease 12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been found in the lung of human COPD patients. MMP408 (14), a potent and selective MMP-12 inhibitor, was derived from a potent matrix metalloprotease 2 and 13 inhibitor via lead ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900093d
更新日期：2009-04-09 00:00:00
abstract：:G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and major targets for drug development. Herein, we sought to identify the regions of the human angiotensin II (AngII) type 1 (hAT(1)) receptor binding cleft that interact with all positions of the AngII using photoaffinity labeling. W...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9015747
更新日期：2010-03-11 00:00:00
abstract：:A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00380a020
更新日期：1985-02-01 00:00:00
abstract：:2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00394a028
更新日期：1987-11-01 00:00:00
